This is a new application for an R01 grant: "Estrogen use in protection from cognitive decline" designed to assess effects of estrogen replacement therapy among postmenopausal women at risk for cognitive decline. We have collected pilot data, which suggest that estrogen use among older persons at risk for Alzheimer's Disease may be protective of regional cerebral metabolism, as measured by position emission tomography with 18-fluorodeoxyglucose (FDG-PET). A total of 71 postmenopausal women ages 50-65, estrogen users, will be randomized to continue or discontinue use and will be followed up to two years for changes in cerebral metabolism and cognitive performance. Subjects will undergo FDG-PET scans and neuropsychological assessments, initially and at the end of the two-year follow-up period. These procedures will allow us to evaluate regional, especially parietal, temporal, and posterior cingulate, cerebral glucose metabolism along with cognitive performance in postmenopausal women at baseline and upon random continuation vs. discontinuation of estrogen replacement therapy. Subjects who to discontinue estrogen use are hypothesized to show more evidence of decline than those who continue do. This project will expand current knowledge of effects of estrogen, by : (1) determining whether estrogen use among postmenopausal women at risk for cognitive decline is protective of brain metabolism;(2) identifying early predictors for cognitive decline;and (3) developing guidelines for estrogen use in postmenopausal women.